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Long-Term Effects of Low-Level Blast Exposure and High-Caliber Weapons Use in Military Special Operators

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Chronic low-level blast exposure has been linked with neurological alterations and traumatic brain injury (TBI) biomarkers. Impaired smooth-pursuit eye movements (SPEM) are often associated with TBI. The purpose of this study was to determine whether long-term operators of low-level blast exposure or high-caliber weapons use displayed oculomotor behaviors that differed from controls. Twenty-six members of an elite military unit performed a computerized oculomotor testing task using an eye tracker and completed a concussion assessment questionnaire. The participants were split into a blast exposure group and control group. The blast exposure group had a history of exposure to low-level blasts or high-caliber weapon use. The results revealed significant differences in SPEM, saccades, and fixations between the blast exposure group and control group. The blast exposure group’s eye movements were slower, stopped at more frequent points when following a target, traveled further from the target in terms of both speed and direction, and showed higher rates of variation and inefficiency. Poor oculomotor behavior correlated with a higher symptom severity on the concussion assessment questionnaire. Military special operators exposed to long-term low-level blasts or high-caliber weapons usage displayed an impaired oculomotor behavior in comparison to controls. These findings further our understanding of the impact of long-term low-level blast exposure on the oculomotor behavior of military special operators and may inform practical implications for military training.
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Citation: Hunfalvay, M.; Murray,
N.P.; Creel, W.T.; Carrick, F.R.
Long-Term Effects of Low-Level Blast
Exposure and High-Caliber Weapons
Use in Military Special Operators.
Brain Sci. 2022,12, 679. https://
doi.org/10.3390/brainsci12050679
Academic Editor: Sergio Bagnato
Received: 2 April 2022
Accepted: 17 May 2022
Published: 23 May 2022
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brain
sciences
Article
Long-Term Effects of Low-Level Blast Exposure and
High-Caliber Weapons Use in Military Special Operators
Melissa Hunfalvay 1, * , Nicholas P. Murray 2, William T. Creel 3and Frederick R. Carrick 4,5,6,*
1RightEye LLC, 7979 Old Georgetown Rd, Suite 801, Bethesda, MD 20814, USA
2Department of Kinesiology, East Carolina University, Minges Coliseum 166, Greensville, NC 27858, USA;
murrayni@ecu.edu
3Neurology Department, Adler University, 17 N Dearborn St, Chicago, IL 60602, USA; wcreel@adler.edu
4Neurology Department, College of Medicine, University of Central Florida, Orlando, FL 32827, USA
5Centre for Mental Health Research in Association with University of Cambridge, Cambridge CB2 1TN, UK
6
Department of Health Professions Education, MGH Institute for Health Professions, Boston, MA 02129, USA
*Correspondence: melissa@righteye.com (M.H.); drfrcarrick@post.harvard.edu (F.R.C.)
Abstract:
Chronic low-level blast exposure has been linked with neurological alterations and trau-
matic brain injury (TBI) biomarkers. Impaired smooth-pursuit eye movements (SPEM) are often
associated with TBI. The purpose of this study was to determine whether long-term operators of low-
level blast exposure or high-caliber weapons use displayed oculomotor behaviors that differed from
controls. Twenty-six members of an elite military unit performed a computerized oculomotor testing
task using an eye tracker and completed a concussion assessment questionnaire. The participants
were split into a blast exposure group and control group. The blast exposure group had a history of
exposure to low-level blasts or high-caliber weapon use. The results revealed significant differences
in SPEM, saccades, and fixations between the blast exposure group and control group. The blast
exposure group’s eye movements were slower, stopped at more frequent points when following a
target, traveled further from the target in terms of both speed and direction, and showed higher rates
of variation and inefficiency. Poor oculomotor behavior correlated with a higher symptom severity on
the concussion assessment questionnaire. Military special operators exposed to long-term low-level
blasts or high-caliber weapons usage displayed an impaired oculomotor behavior in comparison to
controls. These findings further our understanding of the impact of long-term low-level blast expo-
sure on the oculomotor behavior of military special operators and may inform practical implications
for military training.
Keywords: SPEM; smooth-pursuit eye movements; oculomotor; TBI; military
1. Introduction
There has been a growing interest in understanding the effects of long-term low-level
blast exposure and high-caliber weapon use among military personnel due to concern over
potential adverse health outcomes [
1
]. Recent findings suggest that chronic exposure to
low-level blasts may be implicated in neurological alterations and elevated biomarkers
associated with traumatic brain injury (TBI) [2,3].
TBI is a unique and prominent cause of morbidity in military life [
4
,
5
]. Given the
prevalent nature of TBI in military populations, there is an evolving need to understand how
repeated low-level blast exposure and high-caliber weapon use may present an additional
threat to service members’ mental health and well-being. Determining the impact of low-
level blast exposure on cognitive functioning has proven especially challenging given the
evasive nature of concussive injury that is invisible to the eye. However, eye-tracking
technology offers a quantitative, non-invasive, and sensitive solution that can provide a
detailed insight into the brain and cognitive functioning of military personnel following
low-level blast exposure [6].
Brain Sci. 2022,12, 679. https://doi.org/10.3390/brainsci12050679 https://www.mdpi.com/journal/brainsci
Brain Sci. 2022,12, 679 2 of 9
Eye-tracking technology is a uniquely equipped tool for accurately and efficiently
measuring objective TBI biomarkers, including for differentiating the severity of TBI [
7
11
].
Eye tracking has been used to assess neurological functioning, oculomotor assessment,
neurocircuitry abnormalities, and even map oculomotor dysfunction to associated brain
regions [1214].
Oculomotor assessments can be subdivided into discrete eye movements including
smooth pursuits, fixations, and saccades [
15
]. Smooth pursuits use predictive eye-tracking
movements to stabilize a moving target on the fovea, fixations involve maintaining a fixed
eye contact on a visual target input, and saccades are short and quick eye movements
between two points. Collectively, smooth pursuits, fixations, and saccades can reveal
neurological abnormalities through a comprehensive smooth pursuit eye movement (SPEM)
assessment.
The smooth pursuit system is very complex, and while not yet fully understood, it
is what allows humans to predictively track moving objects [
16
18
]. After visual inputs
are processed in the striate cortex, information is relayed to specialized neurons in the
extrastriate areas, which extend to the brainstem and allow communication with the
cerebellum [
17
]. The cerebellum is intimately involved in visual perception and is critical in
generating pursuits [
19
]. The pursuits themselves are primarily controlled by the frontal eye
field and deeper brain structures including the basal ganglia and superior colliculus [17].
Circular smooth pursuits (CSP) have been observed to activate the visual cortex
bilaterally and the right inferior parietal sulcus [
20
]. Neuron firing has also been detected
in the medial temporal lobes and premotor cortex with a marked depressed activity in the
insula and anterior cingulate [
21
]. Evidently, the complexity and breadth of the smooth
pursuit networks makes the system susceptible to damage from TBI.
CSP can be tracked to measure fixation percentages. Concussed individuals have
higher fixation percentages as they are constantly falling behind the target, requiring their
eyes to saccade to catch up to the target [
22
]. Fixation is a conscious process involving
a network of brain regions including the parietal eye field, supplemental eye field, V5
and V5A areas, and the dorsolateral prefrontal cortex [
17
]. The inability to smoothly
track moving objects causes abnormal fixations that may be indicative of damage to these
networks [9].
Variance is another metric that is obtained from tracking CSP. The neurons of the pons
contribute to variance measures, as they are tuned to the eye velocity and can be stimulated
to change the velocity of pursuits. The pontine nuclei project to the cerebellum, which
is involved in the online correction of velocity during pursuit. A high smooth pursuit
variance shows inefficiencies in eye movement that are often indicative of TBI [23].
The saccadic system includes several brain structures including the brain stem, pons,
midbrain, and cerebral cortex [
17
]. Saccades are generated by burst neuron circuits in the
brain stem, which activate motor signals that control the extraocular muscles in the eye [
17
].
Multiple studies have shown that saccadic impairment is associated with TBI [10,24].
More recent approaches to understanding the impact of low-level blast exposure on
brain health have revealed elevated biomarkers associated with traumatic brain injury and
brain diseases in military populations [
3
]. These results further validate efforts towards
identifying objective biomarkers that can inform clinically relevant diagnostic tools.
In contrast, most current methods of TBI diagnosis involve an element of subjectivity
that lacks sensitivity to intricate symptomology [
7
]. The Sport Concussion Assessment Tool
(SCAT) is among the most respected concussion inventories and is widely used by team
physicians [
25
]. The assessment has demonstrated sensitivity and specificity measures
of 96% and 81%, respectively, suggesting a strong validity and reliability [
26
]. However,
advancements in the identification of objective TBI biomarkers will aid in diagnostic
precision while also improving treatment outcomes. This is especially important in a
military setting, where objective TBI biomarkers can inform quick and efficient decision-
making regarding a military personnel’s suitability to perform duties.
Brain Sci. 2022,12, 679 3 of 9
Advancements have been made towards understanding the impact of chronic low-
level blast exposure on military personnel; however, gaps remain. While many studies
have used eye-tracking technology to examine TBI, oculomotor assessment has not been
studied within a military population. Eye-tracking technology provides a unique non-
invasive and quantitative solution for examining the impact of low-level blast exposure
on military members. Therefore, the purpose of this study was to determine whether
long-term operators of low-level blast exposure or high-caliber weapons use displayed
oculomotor behaviors that differed from controls.
2. Materials and Methods
The total number of participants was 25 (between 32–53 years; M= 40.8, SD = 5.76). All
participants were male and members of elite Military units with lengths of service between
10–15 years (M = 13.7, SD = 1.2). The blast exposure group consisted of participants in the
‘Breachers Group’ (BC; n= 9) and ‘Gunners Group’ (GG; n = 9). Controls were in the ‘C
Group’ (CG; n= 7).
Participants were excluded from the study if they met any of the following pre-
screening conditions: neurological disorders (such as known concussion, Parkinson’s
disease); vision-related issues that prevented the successful calibration of all 9 points (such
as extreme tropias, phorias, static visual acuity greater than 20/400, cataracts, consumption
of drugs or alcohol within 24 h of testing) [8,2729].
Participants were selected for the blast exposure group if they had met either of the
following conditions:
1.
Were trained specialty ‘Breachers’ within the Military Unit, where, by virtue of their
job description, to gain entry to locations, they used low-level explosives. These
operatives are therefore exposed to the risk of injury from debris, fragments or whole-
body translation.
2.
Were trained specialty ‘Gunners’ within the Military Unit, where, by virtue of their
job description, they were to operate high-caliber weapons.
Control group participants were Military personnel who were part of the elite units
but were not Breachers or Gunners. All participants did not wear additional protective
headgear beyond the standard helmet.
All participants provided informed consent to participate in this study in accordance
with IRB procedure. All testing was conducted by vision specialists (e.g., optometrists,
ophthalmologists) who had received and passed the RightEye training, education and
protocol procedures prior to testing. Additionally, all data was collected within a morning
session between 8–10 a.m.
Stimuli were presented via the RightEye tests on a Tobii I15 vision 15” monitor fitted
with a Tobii 90 Hz remote eye tracker and a Logitech (model Y-R0017) wireless keyboard
and mouse. The participants were seated in a stationary (non-wheeled) chair that could
not be adjusted in height. They sat in front of a desk in a quiet, private room. Participants’
heads were unconstrained. The accuracy of the Tobii eye tracker was 0.4
within the
desired headbox of 32 cm
×
21 cm at 56 cm from the screen. For standardization of
testing, participants were asked to sit in front of the eye-tracking system at an exact
measured distance of 56 cm, which is the ideal positioning within the headbox range of the
eye tracker.
A Circular Smooth Pursuit (CSP) test was administered to all participants. Participants
were asked to ‘follow the dot, on the screen, as accurately as possible with their eyes as it
moved around in a circle’ (called Circular Smooth Pursuit (CSP)). The dot was 0.2 degrees
in diameter and moved at a speed of 25 degrees of visual angle per second. The tests were
taken with a black background with a white dot and lasted 20 s. The diameter of movement
of the CSP circle was 20 degrees.
Two metrics were used to examine the eye movements while conducting the CSP test
and included:
Brain Sci. 2022,12, 679 4 of 9
Fixation percentage: which accounts for the amount of time that the eye remains still
when it should be following the target. It is measured in milliseconds.
Smooth pursuit variance: the average distance that the eye deviates from the ideal
pathway. It is measured in millimeters.
The Sport Concussion Assessment Tool 2 was administered to all participants [
30
]. The
SCAT is used by healthcare professionals, and is a standardized tool for the acute evaluation
of suspected concussion [
25
]. The SCAT involves 22 questions asking the participant to rate
‘how they feel?’ on a scale of 0 (no symptom) to 1 or 2 (mild symptoms), 3 or 4 (moderate
symptoms), and 5 or 6 (severe symptoms).
The nature of the study was explained to the participants, and all participants provided
informed consent to participate. The study was conducted in accordance with the tenets of
the Declaration of Helsinki. The study protocols were approved by the Institutional Review
Board of East Carolina University. Following informed consent, participants were asked to
complete a pre-screening questionnaire and an acuity vision screening where they were
required to identify 4 shapes at a 4 mm diameter. If any of the pre-screening questions were
answered positively or if any of the vision screening shapes were not correctly identified,
the participant was excluded from the study.
Qualified participants who successfully passed the none-point calibration sequence
completed the eye-tracking test. Written instructions on the screen and animations were
provided before the test to demonstrate the appropriate testing behavior.
Once eye-tracking testing was complete, the participant completed the Sport Concus-
sion Assessment Tool 2 [30].
3. Results
3.1. Data Analysis
The differences in the groups (Control vs. Blast) were analyzed on clinically verified
data using JMP PRO 14.0 (SAS Institute; Cary, NC, USA). All variables were check for
multicollinearity (Table 1). The comparison was evaluated using one-way univariate
ANOVAs on the fixation stability measures, including: Visual Reaction Speed (RS), Fixation
Percentage, Eye-Target Velocity Error, Smooth Pursuit Variance, and Saccadic Velocity. The
alpha level was set at p< 0.05, and partial eta-squared (
ηp2
) was used to determine the
effect size. In addition, a series of receiver operating characteristic (ROC) curve analyses
were plotted for the fixation stability variables. A significant area under the curve (AUC)
with 95% confidence intervals (p< 0.05) was used to indicate the ability of each variable to
differentiate concussed participants from non-concussed ones. A stepwise multivariable
logistic regression model with an expert knowledge approach was used to assess the
relationship between Control and Blast groups and circular smooth pursuit variables:
Visual RS, Fixation Percentage, Eye-Target Velocity Error, Smooth Pursuit Variance, and
Saccadic Velocity. The total number of variables were reduced to avoid collinearity and to
include the variables with the most relevance to the research question. Global effect tests
were used to determine if a predictor was significant at α= 0.05.
Table 1. Strengths of the associations between the various eye-tracking parameters.
1 2 3 4
1. Visual Reaction Speed
2. Fixation Percentage 0.14
3. Smooth Pursuit Variance 0.32 0.46
4. Eye-Target Velocity Error 0.19 0.46 0.47
5. Saccadic Velocity 0.65 0.08 0.53 0.63
3.2. Sport Concussion Assessment Tool 2
Table 2demonstrates a significant increase in SCAT
2 symptom severity and symptom
scores (p= 0.05). For the blast-exposed participants, there was an 18% increase in balance
problems; 20% increase in blurred vision; and approximately a 20% increase in headaches,
Brain Sci. 2022,12, 679 5 of 9
nausea, and light sensitivity. Other increases were seen in neck pain, falling asleep, and eye
strain. The remaining symptoms demonstrated little to no change pre and post exposure.
Table 2. SCAT-2 symptom scores pre and post impact.
Pre-SCAT-2 Symptom
Severity Score
Post-SCAT-2 Symptom
Severity Score
Control 0.40 (SD = 0.89) 0.63 (SD = 1.76)
Blast 20.36 (SD = 15.83) 32.87 (SD = 26.77)
3.3. Fixation Stability Measures Analysis
The ANOVA results for the Visual Reaction Speed and Circular Smooth Pursuit
Fixation Percentage demonstrated a significant main effect for Group [F(1, 24) = 5.336;
p= 0.03,
ηp2
= 0.181] and [F(1, 24) = 10.313; p< 0.001,
ηp2
= 0.301], respectively (see
Table 3). The ANOVA results for the Horizontal Smooth Pursuit Eye-Target Velocity
error demonstrated a significant main effect [F(1, 24) = 6.951; p= 0.04,
ηp2
= 0.22] and
Circular Smooth Pursuit: Smooth Pursuit Variance
[F(1, 24) = 4.069;
p= 0.049,
ηp2
= 0.144].
Further, the data demonstrated a significant effect for Vertical Saccades: Saccadic Velocity
[F(1, 24) = 5.53;
p= 0.027,
ηp2
= 0.187]; however, Targeting Displacement [F(1, 224) = 3.381;
p= 0.067,
ηp2
= 0.293] demonstrated a non-significant difference between the Control and
Blast groups.
Table 3. Mean and standard deviation for fixation stability variables.
Group (n) Visual RS Fixation Percentage Eye-Target
Velocity Error
Smooth Pursuit
Variance Saccadic Velocity
Control 350.13 (51.96) 3.63 (0.721) 17.34 (1.62) 6.88 (3.95) 65.10 (13.96)
Blast Exposure 397.94 (47.31) 4.62 (0.726) 18.61 (0.863) 12.46 (7.306) 51.79 (11.97)
3.4. Multivariable Logistic Regression
A stepwise multiple logistic regression analysis was conducted to evaluate how well
the criterion variable blast status predicted the visual function. The predictors were the five
smooth pursuit indices Visual RS, Fixation Percentage, Eye-Target Velocity Error, Smooth
Pursuit Variance, and Saccadic Velocity, while the criterion variable was Blast status. The
linear combination of Fixation Percentage and Saccadic Velocity was significantly related to
the TBI status,
χ2
= 14.109; p< 0.01, R
2
= 0.459. The other predictors did not significantly
contribute to the model and were removed (see Table 4). The final model accurately
predicted 84.6% of the TBI status, with a sensitivity of 94% and specificity of 63%.
Table 4. Estimated results for model coefficients.
B S.E. Wald df Sig. Exp(B)
Step 1 Fixation Percentage 2.091 0.933 5.021 1 0.025 8.09
Constant 7.786 3.759 4.291 1 0.038 0
Step 2
Fixation Percentage 3.161 1.519 4.33 1 0.037 23.594
Saccadic Velocity 0.169 0.098 2.989 1 0.084 0.844
Constant 2.385 4.658 0.262 1 0.609 0.092
Beta coefficient (B); Standard error (SE); Wald chi-squared test (Wald); Degrees of freedom (df); Statistical
significance (Sig); Odds ratio (Exp(B)).
Among the smooth pursuit parameters, the ROC curves were significant for the
Visual Reaction Speed, Fixation Percentage, and Smooth Pursuit Variance (see Table 5and
Figure 1). The remaining variables did not produce significant ROC curves and produced
low AUC scores.
Brain Sci. 2022,12, 679 6 of 9
Table 5. Summarization of outcomes for the ROC curve analysis.
Variable AUC S.E. p
Visual Reaction Speed
0.706 0.107 0.037
Fixation Percentage 0.785 0.098 0.023
Smooth Pursuit
Variance 0.785 0.104 0.023
Area under the curve (AUC); Standard error (S.E.); Probability value (p).
Brain Sci. 2022, 12, x FOR PEER REVIEW 6 of 9
Among the smooth pursuit parameters, the ROC curves were significant for the Visual
Reaction Speed, Fixation Percentage, and Smooth Pursuit Variance (see Table 5 and Figure 1).
The remaining variables did not produce significant ROC curves and produced low AUC
scores.
Table 5. Summarization of outcomes for the ROC curve analysis
Variable AUC S.E. p
Visual Reaction Speed 0.706 0.107 0.037
Fixation Percentage 0.785 0.098 0.023
Smooth Pursuit Variance 0.785 0.104 0.023
Area under the curve (AUC); Standard error (S.E.); Probability value (p).
Figure 1. ROC for CSP’s: (A) Visual Reaction Time Speed (AUC = 0.706); (B) Fixation Percentage
(AUC = 0.785); (C) Smooth Pursuit Variance (AUC = 0.785).
4. Discussion
The aim of this study was to determine whether long-term operators of low-level
blast exposure or high-caliber weapons use displayed oculomotor behaviors that differ
from controls. This was the first study to assess SPEM, saccades, and fixations within a
military population exposed to repeated low-level blasts and high-caliber weapon use.
The results revealed significant differences in SPEM, saccades, and fixations between the
blast exposure group and control group. There was no significant difference between
groups for targeting displacement. The results demonstrate that, in comparison to the con-
trol group, the blast exposure groups eye movements were slower, stopped at more fre-
quent points when following a target, traveled further from the target in both speed and
direction, and showed higher rates of variation and inefficiency.
Oculomotor behavior has emerged as a sensitive biomarker for TBI, with an ability
to differentiate the diagnosis severity [8]. The CSP is the ability to follow a target around
Figure 1.
ROC for CSP’s: (
A
) Visual Reaction Time Speed (AUC = 0.706); (
B
) Fixation Percentage
(AUC = 0.785); (C) Smooth Pursuit Variance (AUC = 0.785).
4. Discussion
The aim of this study was to determine whether long-term operators of low-level
blast exposure or high-caliber weapons use displayed oculomotor behaviors that differ
from controls. This was the first study to assess SPEM, saccades, and fixations within a
military population exposed to repeated low-level blasts and high-caliber weapon use. The
results revealed significant differences in SPEM, saccades, and fixations between the blast
exposure group and control group. There was no significant difference between groups for
targeting displacement. The results demonstrate that, in comparison to the control group,
the blast exposure group’s eye movements were slower, stopped at more frequent points
when following a target, traveled further from the target in both speed and direction, and
showed higher rates of variation and inefficiency.
Oculomotor behavior has emerged as a sensitive biomarker for TBI, with an ability to
differentiate the diagnosis severity [
8
]. The CSP is the ability to follow a target around in
a circle while minimizing the amount of time that the eye remains still. Previous studies
have observed that individuals with a TBI have longer fixation percentages when engaging
in CSP [22]. The blast exposure group stopped moving their eyes significantly more often
when compared to the controls. This dysfunction is implicated in frontal lobe planning
and decision-making activities, only evident when a decision is required. These findings
Brain Sci. 2022,12, 679 7 of 9
contribute to a clearer understanding of the impact that chronic low-level blast exposure
has on the CSP fixation percentages of military personnel.
Variance in CSP is tracked in three segments of the pathway including middle,
left/right, and up/down. Intact vestibulo-ocular reflexes require efficient functioning
in a network of brain regions that spans the parietal and occipital lobes, premotor cortex,
and brainstem. Inefficient, high-variance eye movements are often indicative of TBI in these
regions [
7
]. The blast exposure groups had more than twice as much variation from the
target than the control group when engaged in smooth pursuit activity. This data provides
new insight into the relationship between repetitive low-level blast exposure and smooth
pursuit variance in military populations.
The results revealed that the blast exposure group was significantly slower than the
control group when engaged in saccadic eye movements. The slow saccadic eye movements
suggest that the blast exposure group had difficulty rapidly and efficiently moving their
eyes between targets. This is notable considering that multiple studies have observed a
relationship between impaired saccadic eye movements and TBI [
10
,
24
]. These findings
shed light on the potential for long-term low-level blast exposure to compromise the
saccadic eye movements of military special operators.
Collectively, the significant differences in SPEM, fixations, and saccades observed in
the blast exposure group are suggestive of TBI symptomology. This assertion is in line with
prior research suggesting that compromised saccades, fixations, and smooth pursuits are
implicated in TBI [
9
]. Unsurprisingly, poor oculomotor behavior in the blast exposure group
was correlated with a higher symptom severity on the SCAT in comparison to the controls.
Symptom severity was most evident through increased balance problems, blurred vision,
headaches, nausea, and light sensitivity. The accuracy of the model was 84.6%, which
suggests an excellent fit. Everything included, the data should be taken into account when
considering the impact of long-term low-level blast exposure and high-caliber weapon use
on the brain health of military personnel.
Practical implications converge on data that supports the refinement of military protec-
tive gear in addition to providing evidence of an objective TBI biomarker that can identify
those with effects from being exposed to low-level blasts and higher caliber weapons train-
ing. Notably, our findings build on existing evidence that suggests neurological alterations
may be implicated in chronic exposure to low-level blasts [
2
]. The military may benefit
from using this data to inform interventions that better protect the neurological health of
its service members.
Limitations of the current study include the fact that all 25 participants were male.
However, this factor was unavoidable given a current restriction on women serving within
the military units of the target population. A second limitation involves the CG’s exposure
to low-level blasts. While the CG participants were not trained as Breachers or Gunners,
most military personnel will have some exposure to blasts throughout their career, making
it challenging to control for this variable. Additionally, factors such as smoking, medication
use, and deployment history are unknown. It could be argued that the sample size is
small; however, the employed model differentiated the blast exposure group from the
control group and was substantiated by the overall statistical power of the test. Lastly, a
potential limitation is the use of a stepwise regression, which has been criticized by some
statisticians. A stepwise regression can be especially problematic with a large number of
predictor variables; however, our variable selection was based originally on an expertise
model and standard data reduction procedure. The final regression, albeit stepwise, does
align with our previous work and is supported by the outcome of the ROC analysis.
5. Conclusions
This study was the first to examine the impact of long-term low-level blast exposure
on the oculomotor behavior of military special operators. Future research should consider
splitting the blast exposure group in order to discern whether oculomotor behavior differs
between groups exposed to long-term low-level blasts and high-caliber weapon use. In
Brain Sci. 2022,12, 679 8 of 9
conclusion, the results of the study found that the oculomotor behavior of military spe-
cial operators exposed to long-term low-level blast exposure or high-caliber weapon use
differed significantly from controls in (a) CSP fixation percentages, (b) CSP variance, and
(c) saccadic eye movements, while poor oculomotor behavior was significantly correlated
with a higher symptom severity on the SCAT.
Author Contributions:
M.H., N.P.M., W.T.C. and F.R.C. contributed to the conceptualization, method-
ology, validation, formal analysis, and writing (original draft preparation and review and editing).
The supervision and project administration was completed by M.H. All authors have read and agreed
to the published version of the manuscript and have contributed substantially to the reported work.
Funding: This research received no external funding.
Institutional Review Board Statement:
The study was conducted in accordance with the Declaration
of Helsinki, and approved by the Institutional Review Board of East Carolina University (UMCIRB
18-000912, 1 June 2018).
Informed Consent Statement:
Informed consent was obtained from all subjects involved in
the study.
Data Availability Statement: The authors will make the data available should someone request it.
Conflicts of Interest:
Melissa Hunfalvay is a full-time employee with RightEye, LLC, and has relevant
affiliations and financial involvement. Nick Murray, William Creel and Frederick Robert Carrick have
no relevant affiliations or involvement.
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... These injuries involve mechanical deformation of blood vessels, transient or persistent blood-brain barrier (BBB) disruption, vasospasm, and microhemorrhages, all of which may remain subclinical but accumulate over time [9,[22][23][24][25][26][27][28]. Findings from both clinical and experimental work indicate a continuum of blast-related pathophysiology, wherein repeated low-intensity insults can induce immediate subclinical disturbances that progress to overt and persistent neurological damage [29][30][31][32][33][34][35]. Each additional exposure appears to heighten the brain's vulnerability to further injury and diminish its recovery capacity [11,17,36,37], placing those who experience frequent blasts at a substantially increased risk of chronic functional deficits and eventual progression to neurodegenerative conditions [38,39]. ...
Article
Full-text available
Repeated exposure to low-level blast overpressure, frequently experienced during explosive breaching and heavy weapons use in training and operations, is increasingly recognised as a serious risk to the neurological health of military personnel. Although research on the underlying pathobiological mechanisms in humans remains limited, this study investigated the effects of such exposure on circulating molecular biomarkers associated with inflammation, neurovascular damage, and endothelial injury. Blood samples from military breachers were analysed for myeloperoxidase (MPO), matrix metalloproteinases (MMPs), and junctional proteins indicative of blood–brain barrier (BBB) disruption and endothelial damage, including occludin (OCLN), zonula occludens-1 (ZO-1), aquaporin-4 (AQP4), and syndecan-1 (SD-1). The results revealed significantly elevated levels of MPO, MMP-3, MMP-9, and MMP-10 in breachers compared to unexposed controls, suggesting heightened inflammation, oxidative stress, and vascular injury. Increased levels of OCLN and SD-1 further indicated BBB disruption and endothelial glycocalyx degradation in breachers. These findings highlight the potential for chronic neurovascular unit damage/dysfunction from repeated blast exposure and underscore the importance of early targeted interventions—such as reducing oxidative stress, reinforcing BBB integrity, and managing inflammation—that could be essential in mitigating the risk of long-term neurological impairment associated with blast exposure.
... highlights the cumulative and insidious effects of repeated low-level blast exposure on the central nervous system (CNS) [6][7][8][9][10][11]. Chronic exposure to blast waves is associated with transient neurological symptoms as well as enduring structural and functional brain changes, contributing to persistent neuroinflammation, long-term cognitive impairments, and an elevated risk of neurodegenerative conditions [12][13][14][15][16][17][18]. An emerging focus in neurotrauma research is the role of autoantibodies targeting brain-specific proteins-such as glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens-in the pathophysiology of repetitive head impacts and blast-induced neurotrauma [19][20][21][22][23][24][25][26][27]. ...
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Full-text available
Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. In this study, we compared circulating autoantibody profiles in military breachers (n = 18) with extensive blast exposure against unexposed military controls (n = 19). Using high-sensitivity immunoassays, we quantified IgG and IgM autoantibodies targeting glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens. Breachers exhibited significantly elevated levels of anti-GFAP IgG (p < 0.001) and anti-PIT IgG (p < 0.001) compared to controls, while anti-MBP autoantibody levels remained unchanged. No significant differences were observed for any IgM autoantibody measurements. These patterns suggest that repetitive blast exposure induces a chronic, adaptive immune response rather than a short-lived acute phase. The elevated IgG autoantibodies highlight the vulnerability of astrocytes, myelin, and the hypothalamic–pituitary axis to ongoing immune-mediated injury following repeated blast insults, likely reflecting sustained blood–brain barrier disruption and neuroinflammatory processes. Our findings underscore the potential of CNS-targeted IgG autoantibodies as biomarkers of cumulative brain injury and immune dysregulation in blast-exposed populations. Further research is warranted to validate these markers in larger, more diverse cohorts, and to explore their utility in guiding interventions aimed at mitigating neuroinflammation, neuroendocrine dysfunction, and long-term neurodegenerative risks in military personnel and similarly exposed groups.
Article
Background Oculomotor and reaction time tests are frequently used assessments of vestibular symptoms, traumatic brain injury (TBI), or other neurological disorders in both clinical and research contexts. When interpreting these tests it is important to have a reference interval (RI) as a comparison for what constitutes a typical/expected response; however, the current body of research has only limited information regarding normative ranges calculated according to established standards or for a military-specific sample. Purpose The purpose of the present study was to describe RIs for oculomotor and reaction time tests in a cohort of service members and veterans (SMVs) for use as comparators by clinicians and scientists. Research Design Descriptive. Study Sample Participants were prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence 15-year Longitudinal Traumatic Brain Injury Study. Only SMVs without a history of TBI or blast exposure were included in the RI calculations. Data Collection and Analysis The test paradigms included in this analysis were: smooth pursuit, prosaccades, antisaccades, saccades and reaction time, predictive saccades, optokinetic nystagmus, auditory reaction time, and visual reaction time. Nonparametric methods, based on the U.S. Food and Drug Administration's recognized consensus standards, were used to calculate 95% RIs. A comparison between the calculated RIs and those available from previously published research is provided. Results Summary statistics and RIs were calculated for 47 outcome parameters from 13 oculomotor and reaction time tests. Sample sizes and age ranges varied across outcome parameters depending on the availability of reference values for RI calculations. The sample sizes used to calculate RIs ranged from 51 to 69. The age of SMVs included in each RI ranged from 19 to 61 years with mean ages ranging from 37 to 39 years. Similarities/differences between the RIs in the present study and those in previously published research are highly dependent on the outcome parameter; however, in general, the RIs in the present study tended to be somewhat wider. Conclusions The RIs provided in this paper can serve as comparisons for clinicians and scientists who are utilizing these oculomotor and reaction time testing paradigms in similar cohorts of patients or research participants.
Article
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Aim Deficits in smooth-pursuit eye movements (SPEM) are often associated with mild traumatic brain injury(TBI). Eye tracking tests serve as a quick objective clinical tool to assess such predictive visual tracking. In this study, SPEM was assessed along circular, horizontal and vertical trajectories in adolescents with concussion and age-matched controls. Methods Ninety-one young adolescents with concussion and 140 visually healthy age-matched controls with a mean age of 14 years performed a computerized test of circular, horizontal and vertical tracking task using an eye tracker. Oculomotor tracking was assessed by computing the rate of fixation, saccades and SPEM made while performing the tasks. Results The predictive visual tracking task was able to differentiate the TBI group from the non-TBI group. The TBI group showed a significant difference in the fixation, saccades and SPEM percentages for circular tracking movement compared to the controls. There was a significant difference in fixation and SPEM % for horizontal and vertical tracking. Conclusions Predictive visual tracking, assessed using eye tracking technology, is able to differentiate deficits in oculomotor functions in individuals with and without concussion. The eye tracking technology may serve as a quick objective tool to detect and monitor neural deficits due to TBI.
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Eye movements measured by high precision eye-tracking technology represent a sensitive, objective, and non-invasive method to probe functional neural pathways. Oculomotor tests (e.g., saccades and smooth pursuit), tests that involve cognitive processing (e.g., antisaccade and predictive saccade), and reaction time tests have increasingly been showing utility in the diagnosis and monitoring of mild traumatic brain injury (mTBI) in research settings. Currently, the adoption of these tests into clinical practice is hampered by a lack of a normative data set. The goal of this study was to construct a normative database to be used as a reference for comparing patients’ results. Oculomotor, cognitive, and reaction time tests were administered to male and female volunteers, aged 18–45, who were free of any neurological, vestibular disorders, or other head injuries. Tests were delivered using either a rotatory chair equipped with video-oculography goggles (VOG) or a portable virtual reality-like VOG goggle device with incorporated infrared eye-tracking technology. Statistical analysis revealed no effects of age on test metrics when participant data were divided into pediatric (i.e.,18–21 years, following FDA criteria) and adult (i.e., 21–45 years) groups. Gender (self-reported) had an effect on auditory reaction time, with males being faster than females. Pooled data were used to construct a normative database using 95% reference intervals (RI) with 90% confidence intervals on the upper and lower limits of the RI. The availability of these RIs readily allows clinicians to identify specific metrics that are deficient, therefore aiding in rapid triage, informing and monitoring treatment and/or rehabilitation protocols, and aiding in the return to duty/activity decision. This database is FDA cleared for use in clinical practice (K192186).
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Importance There is a scientific and operational need to define objective measures of exposure to low-level overpressure (LLOP) and concussion-like symptoms among persons with specialized occupations. Objective To evaluate serum levels of neurotrauma biomarkers and their association with concussion-like symptoms reported by LLOP-exposed military and law enforcement personnel who are outwardly healthy and cleared to perform duties. Design, Setting, and Participants This retrospective cohort study, conducted from January 23, 2017, to October 21, 2019, used serum samples and survey data collected from healthy, male, active-duty military and law enforcement personnel assigned to operational training at 4 US Department of Defense and civilian law enforcement training sites. Personnel aged 18 years or older with prior LLOP exposure but no diagnosed traumatic brain injury or with acute blast exposure during sampling participated in the study. Serum samples from 30 control individuals were obtained from a commercial vendor. Main Outcomes and Measures Serum levels of glial fibrillary acidic protein, ubiquitin carboxyl hydrolase (UCH)-L1, neurofilament light chain, tau, amyloid β (Aβ)-40, and Aβ-42 from a random sample (30 participants) of the LLOP-exposed cohort were compared with those of 30 age-matched controls. Associations between biomarker levels and self-reported symptoms or operational demographics in the remainder of the study cohort (76 participants) were assessed using generalized linear modeling or Spearman correlations with age as a covariate. Results Among the 30 randomly sampled participants (mean [SD] age, 32 [7.75] years), serum levels of UCH-L1 (mean difference, 4.92; 95% CI, 0.71-9.14), tau (mean difference, 0.16; 95% CI, −0.06 to 0.39), Aβ-40 (mean difference, 138.44; 95% CI, 116.32-160.56), and Aβ-42 (mean difference, 4.97; 95% CI, 4.10-5.83) were elevated compared with those in controls. Among the remaining cohort of 76 participants (mean [SD] age, 34 [7.43] years), ear ringing was reported by 44 (58%) and memory or sleep problems were reported by 24 (32%) and 20 (26%), respectively. A total of 26 participants (34%) reported prior concussion. Amyloid β-42 levels were associated with ear ringing (F1,72 = 7.40; P = .008) and memory problems (F1,72 = 9.20; P = .003). Conclusions and Relevance The findings suggest that long-term LLOP exposure acquired during occupational training may be associated with serum levels of neurotrauma biomarkers. Assessment of biomarkers and concussion-like symptoms among personnel considered healthy at the time of sampling may be useful for military occupational medicine risk management.
Article
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Introduction Recently, there has been increasing concern about the adverse health effects of long-term occupational exposure to low-level blast in military personnel. Occupational blast exposure occurs routinely in garrison through use of armaments and controlled blast detonations. In the current study, we focused on a population of breaching instructors and range staff. Breaching is a tactical technique that is used to gain entry into closed spaces, often through the use of explosives. Materials and Methods Initial measurements of blast overpressure collected during breaching courses found that up to 10% of the blasts for range staff and up to 32% of the blasts for instructors exceeded the recommended 3 psi exposure limit. Using a cross-sectional design, we used tests of balance, ataxia, and hearing to compare a sample of breachers (n = 19) to age-and sex-matched military controls (n = 19). Results There were no significant differences between the two groups on the balance and ataxia tests, although the average scores of both groups were lower than would be expected in a normative population. The prevalence of hearing loss was low in the breacher group (4 of 19), and hearing thresholds were not significantly different from the controls. However, the prevalence of self-reported tinnitus was significantly higher in the breacher group (12 of 19) compared with the controls (4 of 19), and all breachers who were identified as having hearing loss also reported tinnitus. Conclusions Our results suggest that basic tests of balance, ataxia, and hearing on their own were not sensitive to the effects of long-term occupational exposure to low-level blast. Some of the blast exposure levels exceeded limits, and there was a significant association of exposure with tinnitus. Future studies should supplement with additional information including exposure history and functional hearing assessments. These findings should be considered in the design of future acute and longitudinal studies of low-level blast exposure.
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Objectives: Traumatic brain injury (TBI) is an increasingly significant health concern worldwide, compounded by the difficultly in detection and diagnosis. Fortunately, a growing body of research has identified oculomotor behavior, specifically fixations, saccades and smooth pursuit eye movements as a promising endophenotype for neurotrauma. To date, limited research exists using fixation stability in a comparative study to indicate the presence of a mild TBI (mTBI), especially in the pediatric population. Methods: The present study examined data from 91 individuals clinically diagnosed with mTBI and a further 140 age- and gender-matched controls. They all completed the RightEye fixation stability test using a remote eye tracker. Participants were compared on five fixation metrics: Bivariate Contour Ellipse Area (BCEA), Convergence Point, Depth, Disassociated Phoria, and Targeting Displacement. Results: Results were analyzed using one-way univariate ANOVAs, ROC analysis, and stepwise logistic regression. BCEA results revealed significant differences between groups with the mTBI group showing a larger gaze spread, indicative of less ability to keep the eyes close to the target without deviating. Conclusions: Fixation stability is detrimentally impacted by mTBI in pediatric patients, and the oculomotor test can be used to differentiate between those with and without an mTBI.
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ImportanceChildren have the highest incidence of mild traumatic brain injury (mTBI) in the United States. However, mTBI, specifically pediatric patients with mTBI, are notoriously difficult to detect, and with a reliance on traditional, subjective measurements of eye movements, the subtle but key oculomotor deficits are often missed.Objective The purpose of this project is to determine if the combined measurement of saccades, smooth pursuit, fixations and reaction time represent a biomarker for differentiating pediatric patients with mild traumatic brain injury compared to age matched controls.DesignThis study used cross-sectional design. Each participant took part in a suite of tests collectively labeled the “Brain Health EyeQ” to measure saccades, smooth pursuit, fixations and reaction time.ParticipantsThe present study recruited 231 participants – 91 clinically diagnosed with a single incident mTBI in the last 2 days as assessed by both the Glasgow Coma Scale (GCS) and Graded Symptoms Checklist (GSC), and 140 age and gender-matched controls (n = 165 male, n = 66 female, M age = 14.20, SD = 2.78).ResultsOne-way univariate analyses of variance examined the differences in performance on the tests between participants with mTBI and controls. ROC curve analysis examined the sensitivity and specificity of the tests. Results indicated that together, the “Brain Health EyeQ” tests were successfully able to identify participants with mTBI 75.3% of the time, providing further validation to a growing body of literature supporting the use of eye tracking technology for mTBI identification and diagnosis.
Article
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Aim: Neural deficits were measured via the eye tracking of vertical smooth pursuit (VSP) as markers of traumatic brain injury (TBI). The present study evaluated the ability of the eye tracking tests to differentiate between different levels of TBI severity and healthy controls. Methodology: Ninety-two individuals divided into four groups (those with mild, moderate or severe TBI and healthy controls) participated in a computerized test of VSP eye movement using a remote eye tracker. Results: The VSP eye tracking test was able to distinguish between severe and moderate levels of TBI but unable to detect differences in the performance of participants with mild TBI and healthy controls. Conclusion: The eye-tracking technology used to measure VSP eye movements is able to provide a timely and objective method of differentiating between individuals with moderate and severe levels of TBI.
Article
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Mild traumatic brain injury (mTBI), or concussion, occurs following a direct or indirect force to the head that causes a change in brain function. Many neurological signs and symptoms of mTBI can be subtle and transient, and some can persist beyond the usual recovery timeframe, such as balance, cognitive or sensory disturbance that may pre-dispose to further injury in the future. There is currently no accepted definition or diagnostic criteria for mTBI and therefore no single assessment has been developed or accepted as being able to identify those with an mTBI. Eye-movement assessment may be useful, as specific eye-movements and their metrics can be attributed to specific brain regions or functions, and eye-movement involves a multitude of brain regions. Recently, research has focused on quantitative eye-movement assessments using eye-tracking technology for diagnosis and monitoring symptoms of an mTBI. However, the approaches taken to objectively measure eye-movements varies with respect to instrumentation, protocols and recognition of factors that may influence results, such as cognitive function or basic visual function. This review aimed to examine previous work that has measured eye-movements within those with mTBI to inform the development of robust or standardized testing protocols. Medline/PubMed, CINAHL, PsychInfo and Scopus databases were searched. Twenty-two articles met inclusion/exclusion criteria and were reviewed, which examined saccades, smooth pursuits, fixations and nystagmus in mTBI compared to controls. Current methodologies for data collection, analysis and interpretation from eye-tracking technology in individuals following an mTBI are discussed. In brief, a wide range of eye-movement instruments and outcome measures were reported, but validity and reliability of devices and metrics were insufficiently reported across studies. Interpretation of outcomes was complicated by poor study reporting of demographics, mTBI-related features (e.g., time since injury), and few studies considered the influence that cognitive or visual functions may have on eye-movements. The reviewed evidence suggests that eye-movements are impaired in mTBI, but future research is required to accurately and robustly establish findings. Standardization and reporting of eye-movement instruments, data collection procedures, processing algorithms and analysis methods are required. Recommendations also include comprehensive reporting of demographics, mTBI-related features, and confounding variables.
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Background: Eye tracking tests to measure horizontal and vertical saccades as a proxy for neural deficits associated with TBI were evaluated in the present study. Methodology: 287 participants reporting either no TBI, mild, moderate or severe TBI participated in a suite of eye tracking tests to measure horizontal and vertical saccadic performance. Results: The horizontal saccades test offered a sensitivity of 0.77 and a specificity of 0.78, similarly the vertical saccades tests offered a sensitivity of 0.64 and a specificity of 0.65. Conclusions: The results indicated that using eye-tracking technology to measure these metrics offers an objective, reliable and quantifiable way of differentiating between individuals with different severities of TBI, and those without a TBI.
Book
Eye Movement Disorders, by Dr. Agnes Wong, fills a great void in the Ophthalmology and Neurology literature by presenting eye movement disorders in a full-color, highly illustrative format. This text explains eye movement disorders in a concise yet comprehensive manner, which makes it an excellent reference book and an outstanding learning text for anyone trying to master the intricate relationship between eye movement disorders, and their underlying neuroanatomy and pathophysiology. Its easy-to-read and user-friendly approach will appeal to specialists in Ophthalmology, Neurology, and Neurosurgery who need a rapid reference on less familiar clinical problems. Key features include: Provides a coherent, concise, and easy to assimilate description and explanation of different eye movement disorders Presents over 100 full-color clinical photographs, radiographs, and color illustrations highlighting pertinent anatomy and brain pathways Highlights key information and important features through boxes, tables, and algorithms